Stereoselective innovative synthesis and biological evaluation of new real carba analogues of minimal epitope Man α(1,2) Man as DC-SIGN inhibitors
Articolo
Data di Pubblicazione:
2016
Citazione:
Stereoselective innovative synthesis and biological evaluation of new real carba analogues of minimal epitope Man α(1,2) Man as DC-SIGN inhibitors / V. Bordoni, V. Porkolab, S. Sattin, M. Thépaut, I. Frau, L. Favero, P. Crotti, A. Bernardi, F. Fieschi, V. Di Bussolo. - In: RSC ADVANCES. - ISSN 2046-2069. - 6:92(2016), pp. 89578-89584. [10.1039/c6ra20401e]
Abstract:
Antagonists of the C-type lectin DC-SIGN are promising therapeutic agents against viruses and bacteria. The development of glycomimetic ligands for DC-SIGN has so far proved to be challenging, since this membrane-protein presents four carbohydrate-binding domains (CRD) that specifically recognize mannose and fucose. In the recent past, we were able to develop inhibitors mimicking the minimal natural epitope Manα(1,2)Man using a mannoside with conformationally restricted dimethyl cycloexandicarboxylate-based aglycons designed to exploit the high enzymatic stability and to generate multivalent or solid supported systems as potent lectin ligands. Herein we describe the innovative synthesis of a different class of pseudodisaccharides, mimics of the natural Manα(1,2)Man moiety, characterized by the presence of a real d-carbamannose unit instead of a simpler mimic structure. Their chemical synthesis and biological activity using an SPR inhibition assay are reported. These pseudodisaccharides display inhibition values similar to those of the natural disaccharide Manα(1,2)Man, with a good affinity for DC-SIGN and can be considered as possible candidates for further structural modifications towards improved inhibitors.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
chemistry (all); chemical engineering (all)
Elenco autori:
V. Bordoni, V. Porkolab, S. Sattin, M. Thépaut, I. Frau, L. Favero, P. Crotti, A. Bernardi, F. Fieschi, V. Di Bussolo
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